The present invention relates to styrene derivatives and polystyrene derivatives used as biomedical substances, in particular materials for cell culture as well as a method for preparing these derivatives.
Owing to the progress in cell culture techniques, considerable progress has been made in studies on the mechanisms of proliferation, differentiation, aging, oncogenesis or the like of cells. In addition, biologically active substances such as vaccins, hormones and interferons have correspondingly been produced. Moreover, it is expected that the production of biological artificial organs such as artificial livers, blood vessels and skin could be developed on the basis of experimental results on culture of various cells such as liver cells, blood vessel wall cells and fibroblast cells of the skin. It is very important to cultivate cells for the purpose of allowing cells to develop a variety of their functions in vitro for a long period of time.
Liver cells by way of an example is specifically explained in more detail to make this point clear. The liver is the greatest glanderous organ of vertebrate animals and is a metabolic center which performs most part of metabolism and regulation thereof. The liver cells originally have long life time over several years and potential ability of proliferation so that they can actively proliferate when a part thereof is accidentally removed. However, if they are cultured in vitro, the life time thereof is greatly shortened, they show almost no proliferation ability and their metabolic activity is rapidly reduced. In general, the culture of cells requires the use of a solid surface to which the cells are adhered when they are cultivated. The liver cells hardly adhere to the surface of usually employed culture dishes of glass or polystyrene which have been surface-treated. Therefore, it has long been desired to develop biomedical materials which make it possible to cause adhesion and proliferation of these cells while maintaining the functions thereof.
Recently, as the mechanisms of cell adhesion, of information transmission through a cell membrane or the like are elucidated at molecular level, it has become clear that sugar chains which exist on the surface of cell membranes in the forms of glycoproteins or glycolipids play an important role in recognizing ability of the cells.
The inventors of this invention already synthesized polystyrenes having monosaccharide or oligosaccharide residues such as glycose, maltose, lactose and maltotriose residues on the side chains and tried to adhere rat liver cells to the surface of a culture dish to which a film of such a polystyrene had been applied. As a result, it is found that the polystyrene film having lactose residues on the side chains, among others, substantially increases the ability of the liver cells to adhere to the surface of a culture dish irrespective of the presence of serum. Thus, these polymers show excellent properties as hybrid type biomedical materials (see "Japanese Journal of Polymer Science and Technology", 1985, Vol. 42, No. 11, pp. 719-724).
As explained above, these polystyrenes having monosaccharide or oligosaccharide residues on the side chains show excellent cell-recognizing ability. As a result, they make it possible to cause good adhesion and proliferation of specific cells such as liver cells. However, they do not serve to adhere and proliferate other cells. For this reason, it has been desired to develop various biomedical materials which exhibit ability of adhering and proliferating other cells and hence have wide variety of applications.